Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

The use of semiquantitative technique of inductively coupled plasma mass spectrometry (SQ-ICP-MS) analysis in the study of trace elements concentration in environmental samples

Oznaczenia pierwiastków śladowych z wykorzystaniem spektrometrii mas z plazmą wzbudzoną indukcyjnie (ICP-MS) są popularne w laboratoriach w kraju i za granicą. ICP-MS stanowi rutynową metodę w analizie różnych rodzajów próbek, a w tym próbek środowiskowych; rekomendowana jest w wielu przypadkach przez Amerykańską Agencję Ochrony Środowiska (EPA). Stwarza ona możliwość wykonania oznaczeń wielu pierwiastków jednocześnie z dużą dokładnością i precyzją, jednak wymaga podczas kalibracji użycia metody wzorca zewnętrznego. Gdy uzyskanie wysokiej dokładności pomiarów nie jest wymagane (np. w tzw. badaniach przesiewowych), możliwe jest wykorzystanie techniki półilościowej (ang. semiquantitative - SQ) ICP-MS. SQ-ICP-MS daje możliwość pominięcia etapu kalibracji z użyciem wzorców zawierających wszystkie oznaczane pierwiastki, przez co oszczędza się czas oraz odczynniki. Dokładność SQ-ICP-MS mieści się zwykle w przedziale 30-50%. Technika ta jest głównie wykorzystywana w sytuacjach, gdy niedostępny jest odpowiedni wzorzec kalibracyjny oraz w przypadkach analizy ciał stałych z użyciem ablacji laserowej. SQ-ICP-MS ma duży potencjał aplikacyjny w badaniach przesiewowych, jak np. poszukiwanie roślin akumulujących pierwiastki śladowe. Jej wykorzystanie w wielu przypadkach stanowi rozwiązanie bliższe ideom zielonej chemii analitycznej. Choć technika ta daje duże możliwości, nadal jest mało popularna, nawet wśród specjalistów. Niniejszy artykuł poświęcony jest ocenie tej techniki, wskazuje jej możliwości i ograniczenia, szczególnie w odniesieniu do analiz próbek środowiskowych.Determination of trace elements by inductively coupled plasma mass spectrometry (ICP-MS) is a popular approach used in laboratories all over the world. ICP-MS is a routine method in analysis of different types of samples, including environmental samples and is recommended in many cases by the American Environmental Protection Agency (EPA). It provides the possibility of determining many elements at the same time with a good accuracy and precision, but requires the use of a calibration procedure using external standard calibration. If a high accuracy is not a priority (e.g. during screening tests), a semi-quantitative (SQ-ICP-MS) technique can be used. The SQ-ICP-MS does not require a complicated calibration protocol, which saves time and reagents. The accuracy of SQ-ICP-MS is usually in the range of 30-50%. The SQ-ICP-MS is applied if no calibration standards are available or during solid samples analysis with the use of laser ablation ICP-MS. Semi-quantitative technique has a high application potential in screening tests, such as searching for plants accumulating trace elements. SQ-ICP-MS meets criteria of technique recommended by the green analytical chemistry. Although the technique offers great opportunities, it is not very popular, even among specialists. This article is the critical review of the method, indicates its possibilities and limitations, especially in the context of environmental sample analysis

The study of stable lead isotopes - analytical issues and practical importance

Celem artykułu jest przedstawienie aktualnego stanu wiedzy na temat oznaczeń trwałych izotopów ołowiu oraz możliwości wykorzystania wyników badań w różnych dziedzinach nauki. Skład izotopowy ołowiu oznaczany w różnych próbkach (np. środowiskowych, medycznych, artefaktach archeologicznych) może służyć wyjaśnieniu problemów naukowych z zakresu ochrony środowiska, geologii, kryminalistyki, archeologii, ekologii, nauki o żywieniu i in. Popularność badań trwałych izotopów ołowiu wynika, między innymi, z coraz lepszego dostępu do nowoczesnych technik analitycznych pozwalających na precyzyjny pomiar stężeń izotopów (TIMS, MC-ICP-MS, LA-ICP-MS i in.). W niniejszym artykule skrótowo omówiono metodykę oznaczania trwałych izotopów ołowiu oraz podano przykłady badań stosunków izotopowych ołowiu w różnych dyscyplinach naukowych.The aim of this paper is to present the current knowledge on determination of stable lead isotopes and to discuss the possibility of their application in different scientific disciplines. Lead isotope ratio determined in different kinds of samples (e.g. environmental samples, medical samples, artifacts) may be useful for elucidation of scientific problems in environmental sciences, geology, criminology, arheology, ecology, nutrition sciences etc. Growing popularity of lead isotope ratio studies results from facilitate access to modern analytical techniques that enable precise isotope measurements (TIMS, MC-ICP-MS, LA-ICP-MS etc.). This article briefly discusses the methods used in stable lead isotope determinations and gives examples of the studies carried out by researchers specializing in different scientific disciplines

O empirycznym najlepszym liniowym nieobciążonym predyktorze dla pewnego modelu mieszanego

The problem of small area prediction is considered under a Linear Mixed Model. The article presents a proposal of an empirical best linear unbiased predictor under a model with two correlated random effects. The main aim of the simulation analyses is a study of an influence of the occurrence of a correlation between random effects on properties of the predictor. In the article, an increase of the accuracy due to the correlation between random effects and an influence of model misspecification in cases of the lack of correlation between random effects are analyzed. The problem of the estimation of the Mean Squared Error of the proposed predictor is also considered. The Monte Carlo simulation analyses and the application were prepared in R language.Zagadnieniem poruszanym w artykule jest problem predykcji w przypadku pewnego modelu należącego do klasy liniowych modeli mieszanych. W opracowaniu została przedstawiona propozycja empirycznego najlepszego liniowego nieobciążonego predyktora dla liniowego modelu mieszanego z dwoma skorelowanymi efektami losowymi. Głównym celem opracowania jest symulacyjne zbadanie wpływu występowania zależności między efektami losowymi na własności rozważanego predyktora. W artykule podjęto również problem estymacji błędu średniokwadratowego zaproponowanego predyktora. Badanie symulacyjne oraz przykład przygotowano z użyciem programu R

The use of survey sampling in survey data analyzing. Case study of monitoring epidemic by internet users

Artykuł porusza tematykę monitorowania zjawisk epidemiologicznych wśród internautów. Sklasyfikowano rodzaje źródeł informacji dotyczących epidemiologii w Polsce i zaprezentowano ich przykłady. Autorzy przedstawili wyniki przeprowadzonych badań ankietowych z lat 2013-2015, które nawiązują do tej tematyki. Do analizy danych statystycznych z 2015 roku zastosowano metodę reprezentacyjną. Populację internautów podzielono na warstwy ze względu na: zamieszkiwane województwo, płeć oraz wiek.The article describes topic of Internet usage to monitor epidemic. Polish epidemiological source of information in this area have been classified and its examples have been given. Authors present results of their research conducted in 2013-2015 connected with this subject. Sampling survey method has been used to analyze data obtained in 2015. The division of the population of Internet users was made according: the voivodship, sex and age group